From ‘essential’ hypertension to intensive blood pressure lowering: the pros and cons of lower target values

When towards the end of the Second World War, the ‘big three’, i.e. Franklin D. Roosevelt, Winston Churchill, and Joseph Stalin, met in Yalta from 4 to 11 February 1945, the US President was already a sick man; not a good basis for the reorganization of Europe’s post-war political landscape. Perhaps history might have developed differently would he have been treated as is standard today. Two months later, on 12 April 1945, Franklin D. Roosevelt’s personal physician Admiral McIntyre announced the sudden death of the President and claimed ‘Came out of clear sky. There was no indication of imminent danger.’1 As the media reported the next day. The death of the President had been determined to be due to a cerebral haemorrhage, apparently without any preceding symptoms. Of note, Franklin D. Roosevelt had been known to suffer from so-called ‘essential’ hypertrension for many years and his blood pressure values steadily rose as his presidency was faced with increasing problems with the advent of the Second World War (Figure 1 2). Blood pressure chart of Franklin D. Rososevelt over the years of his presidency (from Messerli2). At that time, high blood pressure was considered ‘essential’ as it was thought to be necessary in such patients to allow for appropriate perfusion of vital organs. Indeed, as late as in 1937, the Braunwald of the day, Paul Dudley White, stated: ‘Hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we could control it’. So they did, and allowed Franklin D. Roosevelt’s blood pressure to rise steadily until a blood vessel in the brain broke. Then of course, there was little that could be done: neither calcium antagonists nor inhibitors of the renin–angiotensin system were available, beta-blockers were only discovered in the 1960s, and the commonly used diuretics were toxic. At some point, the Presidents’ physicians tried Kempner’s rice diet obviously without success. It was the late Edward D. Freis as well as the investigators of the Framingham Study3 who noted in the early 1960s that high blood pressure was indeed not a good thing, but a risk factor for myocardial infarction, stroke, and death. Shortly after this observation, Freis designed and carried out the first randomized, placebo-controlled, double-blind multicentre trial in cardiovascular medicine to prove that blood pressure lowering would prevent such events. Starting in January 1964 over several years a total of 523 patients with high blood pressure were enrolled and treated with either a combination of a thiazide diuretic, reserpine, and hydralazine, or placebo. Out of the 523 patients, 143 had diastolic blood pressures >115 mmHg. In this subgroup, the trial had to be stopped after only 18 months because of a marked reduction in morbidity and mortality in the treated patients.4 Indeed, 4 of the 70 patients in the placeob group died and 21 experienced major cardiovascular events, but none of the 73 treated patients died and only one had severe side effects of the drugs. The remaining 380 patients with diastolic blood pressures between 90 and 114 mmHg were followed for ∼3 years during which 19 died in the placebo group, but only 8 in the active group.5 As expected, these hypertensives died from myocardial infarction, sudden death, or stroke. Overall, 29% of the untreated hypertensives, but only 12% of those recieving drugs, developed cardiovascular events. Thus, Freis for the first time convincingly demonstrated that blood pressure lowering saves lives and reduces devastating complications such as stroke. Surprisingly, his findings did not make the headlines initially, but eventually changed medicine and led to to the concept that high blood pressure was not ‘essential’ (the Germans called it but a cardiovascular risk factor that The of blood pressure should be it to be a to this day. is a blood it in the of mmHg as the or mmHg as the in who as or or is an good for the In the late the on and of Blood considered mmHg as in the values to mmHg were values mmHg as in the values were for some time, until demonstrated that even in this group and even in the of 12 blood pressure lowering to mmHg or even infarction, and the for the of a blood pressure of mmHg for patients and even mmHg in with Indeed, this for the was and only a a for a reduction of Then the trial was in and an in the with some and The of the that they should in a on to and for or an even blood pressure in from of and from of with a of the from the and in an of the in his The in this not those of the of the or of the of The Blood was stopped early because of a reduction in cardiovascular morbidity and mortality lowering blood pressure to and the findings were in a months to the as we it the of and the used in the for of blood pressure the for in to be mmHg and in the and the patients with high for of could be but not any for in Blood enrolled years and in and the Blood patients with and the US of those and the investigators the a standard group an of to a and an group an of to a mmHg. 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